SENS6 Favorites: How small molecule intervention by the Chen and Madeo labs may reverse the aging process

Posted by Iain Inkster on October 16, 2013 | SENS6

 

The SENS6 conference was packed with more exciting presentations and excellent opportunities for networking than I could have imagined. Combined with the legendary University of Cambridge venue, it made for an unforgettable experience. I was excited to have the opportunity to share my 2013 summer research with some of the most prominent scientists in the aging research field.
 

Navneet's SENS6 poster presentation


I’m still amazed how much was covered in just four days of talks. I was particularly drawn to two presentations at the conference, that of Dr. Danica Chen from the University of California, Berkeley and that of Dr. Frank Madeo from the University of Graz. The SENS approach calls for damage repair to maintain and restore cellular function. Both presentations focused on small molecule interventions that could reverse the effects of aging.

Dr. Chen explained how sirtuin 3 (SIRT3) can slow the rate of damage to stem cells. Sirtuins are a group of seven proteins that affect many cellular processes by activating metabolic pathways. For example, sirtuins are believed to play a role in slowing the aging process via calorie restriction. However, a direct role in repair of cellular damage has remained poorly understood until now.

The Chen lab found that SIRT3 activates particular proteins in mitochondria that limit the build-up of reactive oxygen species (ROS). Levels of ROS are known to increase with age and cause oxidative stress, which ultimately damages cellular structures and leads to cell death. Based on this information, Dr. Chen decided to study SIRT3 in hematopoietic (blood) stem cells to see if it contributes to the maintenance of the stem-like properties of these cells, such as self-renewal and differentiation.

Interestingly, loss of SIRT3 in older blood stem cells not only limited their rate of replication but also reduced their ability to self-renew and differentiate. The Chen lab then confirmed that a loss of SIRT3 was strongly correlated with higher levels of oxidative stress. Furthermore, the lab found that SIRT3 interacted with another protein called SOD2 to reduce oxidative stress. Finally, Dr. Chen revealed that overexpression of SIRT3 was sufficient to rescue the damage caused by oxidative stress and restore the cellular function! This paves the way for further research into SIRT3 as a potential rejuvenative treatment.




Another highlight of SENS6 for me wasDr. Frank Madeo’s demonstration that a compound called spermidine promotes longevity. Spermidine belongs to a class of organic compounds known as polyamines, which have been shown to decline with age. They have been identified as key regulators of genes involved in aging, but the specific details as to how they interact with these genes remains unknown.

Dr. Madeo’s lab found that spermidine administered to aging yeast cells not only extended their lifespan but also led to an increased production of naturally occurring spermidine in the cells. A similar result was also observed in both fruit flies and nematodes. Furthermore, the Madeolab demonstrated that mice receiving a regular dose of spermidine for 200 days exhibited a reduction in age-related oxidative damage. Dr. Madeo noted that spermidine treatment promoted autophagy, which is the process of degrading and destroying unneeded cellular components through the lysosome. This discovery is particularly interesting to rejuvenative medicine because diminished autophagic activity is thought to play a crucial role in the aging process.

 


Who would have thought that a single compound such as SIRT3 or spermidine could affect aging so drastically? The conference started out with a bang and got better with each presentation. I left SENS6 with a new appreciation for the progress that has been made in the field of rejuvenation biotechnologies, and I am excited to see what progress we make by SENS7 in 2015!

 

For more on 2013 intern Navneet Ramesh click here